Clonal growth of bovine vascular endothelial cells: fibroblast growth factor as a survival agent. Bovine vascular endothelial cells do not grow when cultured at low density unless fibroblast growth factor is included in the culture medium. When endothelial cells obtained from the intimal surface of fetal and adult aortas were seeded at low density (8 cells per cm2), they formed small colonies of large, irregular, vacuolated cells. At very low density (0.3 cells per cm2) they did not survive. The addition of fibroblast growth factor to endothelial cells maintained at such low densities resulted in the formation of vigorously growing colonies of small, uniform cells. Electron microscopy showed that the cultured endothelial cells had the fine structure characteristics of endothelial cells. Immunofluorescence microscopy revealed antihemophilic factor (Factor VIII) antigen in the cells. Our results demonstrated that fibroblast growth factor permits the survival of endothelial cells plated at extremely low cell density. With the use of fibroblast growth factor, endothelial cell clones are easily produced.


Direct method for detection and characterization of cell surface receptors for insulin by means of 125I-labeled autoantibodies against the insulin receptor. Autoantibodies directed against the cell surface receptors for insulin are found in some patients with extreme insulin resistance. These antibodies specifically inhibit the binding of insulin to its receptor. A purified IgG fraction from one patient's plasma was labeled with 125I. The 125I-labeled antireceptor antibody, which initially represented about 0.3% of the total 125I-IgG, was enriched by selective adsorption and subsequent elution from cells rich in insulin receptors. The 125I-antireceptor antibody bound to cells and the binding was inhibited by whole plasma and purified IgG from this patient, as well as whole plasma from another patient with autoantibodies to the insulin receptor. Insulins that differed 300-fold in biological potency and affinity inhibited binding of 125I-antireceptor antibody in direct proportion to their ability to bind to the insulin receptor. The binding of 125I-antireceptor antibody was closely correlated with the binding of 125I-insulin over a wide range of receptor concentrations on different cell types. Experimentally induced reduction of the insulin receptor concentration was associated with parallel decreases in the binding of 125I-antireceptor antibody and 125I-insulin. The preparation of 125I-antireceptor antibody with a high specific activity by cytoadsorption and elution has provided a sensitive method for the detection of receptors and autoantibodies to cell surface components.


Repair tracts in mismatched DNA heteroduplexes. Heteroduplexes with mismatches at four sites were constructed from separated strands of lambda DNA and used to transfect Escherichia coli under recombinationless conditions. The output phages from 967 single cells in one experiment and 1016 in another were analyzed to determine the pattern of mismatch repair. A wide range of repair frequencies was found among the mismatches studied. Repair involving two or more close sites in the same heteroduplex occurs much more often on thesamestrandthanonopposite strands. Analysis of the pattern of repair suggeststhat repair tracts initiate at mismatches, propagate preferentially in the 5'leads to 3' direction, and extend an average distance of ca 3000 nucleotides.


Allelic heterogeneity within allozymes separated by electrophoresis in Drosophila pseudoobscura. Electrophoretic separation of esterase-5 allozymes of Drosophila pseudoobscura in gels of different acrylamide concentrations and in different buffer systems has revealed the existence of six different alleles within the most frequent class, esterase-5(1.00), and three alleles in the other most frequent class, esterase-5(1.07). Two of the alleles affect subunit binding. Esterase-5 allozyme classes based on electrophoresis in 5% acrylamide gels are therefore highly heterogeneous.


Superstructure of linear duplex DNA.

Superstructure of linear duplex DNA. The superstructure of a covalently closed circular DNA (of bacteriophage PM 2) was compared by electron microscopy with that of a linear duplex DNA (of bacteriophage T7) when ionic strength and benzyldimethylalkylammonium chloride concentration were varied. In parallel studies the sedimentation behavior of these DNAs was studied by analytical ultracentrifugation, but for technical reasons these had to be without benzyldimethylalkylammonium chloride. By combining the information from the two methods one has to conclude that with increasing ionic strength the linear duplex T7 DNA spontaneously forms a structure similar to that of the superhelical structure of closed circular PM 2 DNA. The superstructure is destroyed under premelting conditions and in the presence of an excess of ethidium bromide.


Heat mutagenesis in bacteriophage T4: the transversion pathway. Heat induces transversions (as well as transitions) at G-C base pairs in bacteriophage T4. The target base for transversions is guanine,which is converted to a product which is sometimes replicated and transcribed as a pyrimidine.A model for this process is proposed in which the deoxyguanosine glycosidic bond migrates from N9 to N2: the resulting deoxyneoguanosine may pair with normal guanine to produce G-C leads to C-G transversions.


Identification of prekallikrein and high-molecular-weight kininogen as a complex in human plasma. Prekallikrein and high-molecular-weight kininogen were found associated in normal human plasma at a molecular weight of 285,000 as assessed by gel filtration on Sephadex G-200. The molecular weight of prekallikrein in plasma that is deficient in high-molecular-weight kininogen was 115,000. This prekallikrein could be isolated at a molecular weight of 285,000 after plasma deficient in high-molecular-weight kininogen was combined with plasma that is congenitally deficient in prekallikrein. Addition of purified 125I-labeled prekallikrein and high-molecular-weight kininogen to the respective deficient plasma yielded a shift in the molecular weight of prekallikrein, and complex formation could be demonstrated by incubating prekallikrein with high-molecular weight kininogen. This study demonstrates that prekallikrein and high-molecular-weight kininogen are physically associated in plasma as a noncovalently linked complex and may therefore be adsorbed together during surface activation of Hageman factor. The complex is disrupted when these proteins are isolated by ion exchange chromatography.


Construction of plasmids carrying the cI gene of bacteriophage lambda. By techniques of recombination in vitro, we have constructed a plasmid bearing the repressor gene (cI) of bacteriophage lambda fused to the promoter of the lac operon. Strains carrying this plasmid overproduce lambda repressor. This functional cI gene was reconstituted by joining DNA fragments bearing different parts of that gene. Flush end fusion techniques, involving no sequence overlap, were necessary for the construction; in certain cases, the abutting of the DNA molecules bearing ends generated by different restriction endonucleases creates a sequence at the junction which is recognized by one of the restriction endonucleases.


Infinite allele model with varying mutation rate. Available data suggest that the variation in mutation rate among protein loci follows the gamma distribution. Thus, taking into account this variation, formulae are developed for the distribution of allele frequencies, mean and variance of heterozygosity, expected number of alleles, proportion of polymorphic loci, and genetic distance. These formulae should be more appropriate for the analysis of gene frequency data for protein loci than equivalent formulae with constant mutation rate.


Dichloromethane as an antisickling agent in sickle cell hemoglobin. Microscopic studies of red cells from homozygous sickle cell patients show that dichloromethane does prevent sickle cell formation in vitro and does cause reversion of sickled cells to normal after exposure to dichloromethane. X-ray structural analysis of human deoxyhemoglobin crystals exposed to dichloromethane shows four unique binding sites. Arguments are presented to suggest that the binding site close to tryptophan 14alpha prevents the formation of helical polymers, i.e., prevent sickling.


Rat sympathetic neurons and cardiac myocytes developing in microcultures: correlation of the fine structure of endings with neurotransmitter function in single neurons. Microcultures containing single sympathetic principal neurons and small numbers of dissociated heart myocytes were prepared from newborn rats. After the transmitter properties of the neuron were studied by electrophysiological experiments, the microculture was examined with the electron microscope. Single neurons of either putative cholinergic or putative adrenergic character made morphological synapses on themselves (autapses), although only cholinargic autapses were detected electrophysiologically. Numerous axonal varicosities were present adjacent to the myocytes but no synaptic specializations were evident. After permanganate fixation to localize endogenous norepinephrine, the endings of neurons which appeared to secrete catecholamines contained many small granular vesicles, while the endings of neurons which appeared to secrete acetylcholine contained none. The endings of neurons which apparently secreted both catecholamines and acetylcholine contained only occasional small granular vesicles.


Protein cleavage during virus assembly: a novel specificity of assembly dependent cleavage in bacteriophage T4. Cleavage of precursor proteins occurs during assembly of numerous viruses. Seven bacteriophage T4 head-related proteins areknown to be cleaved during morphogenesis. Sequences surrounding the cleavage sites in T4 head precursors P23 and IPIII are reported here. We previously determined the sequences of precursor and processed forms of IPII and IPI. Cleavage occurs at a glutamyl-alanyl bond in each protein. By comparison of sequences around five cleaved and four uncleaved Glu-Ala bonds in head precursors, it appears that cleavage is limited to the Thr or Ala, and X2 to hydrophilic residues. The results suggest the viral-induced assembly protease recognizes and cleaves an extended primary structure in the structurally dissimilar precursors.


Renal CO2 production from glutamine and lactate as a function of arterial perfusion pressure in dog. The energy cost of renal function in the intact kidney of the dog was assessed at a series of arterial perfusion pressures. Pressure was varied by partially inflating a balloon at the tip of a catheter positioned in the aorta above the origins of the renal arteries. Either L-[U-14C]-lactate was infused intravenously in tracer amounts throughout each experiment. Total renal CO2 production and 14CO2 production from each isotope permitted assessment of total renal oxidative metabolism and the proportions derived from the two major substrates of the kidney. Stepwise inflation of the aortic balloon progressively lowered glomerular filtration rate, renal blood inflow, filtered and consequently reabsorbed Na+, total renal CO2 production, and 14CO2 derived from glutamine and lactate. The percent of total CO2 derived from lactate decreased more or less in proportion to the decrease in percent of total CO2 produced. Results were consistent with the view that reabsorption of sodium is the major energy sink of the kidney. They suggest that the oxidation of glutamine supplies energy for tubular transport and basal demands such as synthesis of hormones and maintenance of structure, whereas the oxidation of lactate supplies energy mainly for transport activities.


Ear and hearing in Sphenodon punctatus.

Ear and hearing in Sphenodon punctatus. Observations on Sphenodon punctatus have revealed new features of the anatomy of the ear,and measurements in a living specimen by means of cochlear potentials show the form and level of this ear's performance in sound reception. For an animal lacking an external ear opening and a functional tympanic membrane, the sensitivity of from 100-900 Hz is surprisingly good in low tones with peak response around 200-400 Hz. The inner ear is well developed, with a tectorial membrane connected to a tectorial plate that extends throughout the cochlea. The best region of sensitivity agrees well with the main frequency components of the animal's vocalizations.


Hemodynamic consequences of circuit weight training.


An instrument for identifying implicit values in physical education programs.


Post-KR delay intervals and mental practice: a test of Adams' closed loop theory.


Leg power and Canadian female volleyball players.


Academic and athletic ability as popularity factors in elementary school children.


Effects of competency-based intervention on student-teacher and pupil behavior.


Separation potential of educable retarded and intellectually normal boys as a function of motor performance.


Comparative perceptions of psychological well-being as influenced by sport experience in female athletes.


Relationship between trait and state anxiety, movement satisfaction, and participation in physical education activities.


Bicycle ergometer endurance in women related to maximal leg force, leg volume, and body composition.


Comparison of three predictors of state anxiety in competitive situations.


Effects of competition upon the aggressive responses of college basketball players and wrestlers.


Fitness, fatness, and serum cholesterol: an epidemiological study of an entire community.


Effects ball and background color have upon the catching performance of elementary school children.


Biomechanics of distance running: a longitudinal study.


Effects of different intensities of exercise on intraocular pressure.


Effect of knowledge of results on attitude formed toward a motor learning task.


Team orientations, interpersonal relations, and team success.


The objectivity, reliability, and validity of the OSU step test for college males.


Children's attitudes toward females in sports: their relationship with sex, grade, and sports participation.


Space utilization: criteria for the selection of playground equipment for children.


Min-by-min respiratory exchange and oxygen uptake kinetics during steady-state exercise in subjects of high and low max VO2.


Force-time parameters and physical growth of boys ages 6 to 12 years.


Work output and heart rate response of top level New Zealand oarsmen.


An instrument for measuring directional movement speed under different environmental stimulus conditions.


Performances by college students in handball being taught by three different teaching methods.


Stabilometer computerized analog recording system for studying gross motor skill learning.


Personality differences of adult men before and after a physical fitness program.


Dynamic balance in preschool children: quantifying qualitative data.


Simple coincidence-anticipation apparatus.


Relationship among submaximal heart rate, aerobic power, and running performance in children.


Normative data for body segment weights, volumes, and densities in cadaver and living subjects.


Electronic metronome for free running subjects.


Psychological scaling of proposed title IX guidelines.


Electronic differentiation of electrogoniometer output.


A multi-purpose sequence timing unit.

A multi-purpose sequence timing unit.


Optimal strategy at decision points in singles squash.


The effectiveness of the "golfer's groove" in improving golfers' scores.


The indebtedness of students currently attending medical school.


Lithium carbonate in Gilles de la Tourette's disease.


Continuing medical education requirements for triennial relicensure in Rhode Island.


Problems in mental health care in Rhode Island.II.Organizing the mental health network in Rhode Island--the state role.


Problems in mental health care in Rhode Island. IV. A reallocation model for limited health resources.


A crisis for program evaluation: an embarrassment of opportunity.


Motilin-induced electrical activity in the canine gastrointestinal tract. Myoelectric activity induced by a synthetic analogue of the duodenal polypeptide motilin, was studied in isolated vascular-perfused canine duodenum and stomach, and in conscious dogs with serosal electrodes implanted in the stomach and the small intestine. In the isolated preparation, the duodenum was found to be four times as sensitive as the antrum to the polypeptide, showing a dose-dependent increase in spike activity within two minutes after administration of the polypeptide. By contrast, in the conscious fasted animal, the only response to motilin, above a threshold dose, was the interpolation of a premature migrating myoelectric complex in the spontaneous interdigestive sequence, appearing fifteen to twenty minutes after the start of infusion. Since the essential difference between the ex vivo and the intact intestine was the preservation of efferent and afferent nervous connections in the latter, it seems that in the conscious animal, the response to exogenous motilin is modulated by the innervation of the intestine, or, alternatively, motilin interacts with the centre controlling the pattern of motor activity in the small intestine rather than directly with smooth muscle. The latter hypothesis is supported by the observation that motilin had no effect on the motor activity of the small intestine during the infusion of pentagastrin which abolishes spontaneous migrating myoelectric complexes.


Syntheses of motilin analogues.

Syntheses of motilin analogues. According to a first suggestion for the primary structure of the gastrointestinal hormone motilin, two analogues containing norleucine and leucine instead of methionine in the sequence position 13 (primarily called 13-norleucine and 13-leucine-motilin) have been synthesized. Both synthetic peptides were biologically active in equivalence to the natural product. A correction of the proposed amino acid sequence became necessary after rechecking the results by comparison with the synthetic materials. The two analogues must therefore correctly be named 13-norleucine-14-desamidomotilin and 13-leucine-14-desamido-motilin.


Measurement of human plasma motilin.

Measurement of human plasma motilin. A specific radioimmunoassay has been developed for human plasma motilin. No cross reaction was seen with other gut hormones and only a single major peak of motilin immunoreactivity was found in plasma and gut extracts after gel chromatography. The motilin content of the human duodenum was 165.7+/-15.9 pmol/g wet weight and jejunum 37.5+/-2.8 pmol/g with negligible amounts in the rest of the gut. Fasting plasma motilin concentrations in 100 healthy subjects ranged from less than 5 to 300 pmol/l (mean 72 pmol/l).


Potentiation between 13-Nle-motilin and acetylcholine on rabbit pyloric muscle in vitro. The interaction of 13-nle-motilin-a synthetic analogue of the natural polypeptide-with acetylcholine was studied on rabbit isolated pyloric sphincter in vitro. Adding subthreshold doses of 13-nle-motilin reduced the calculated acetylcholine dose for half maximal contraction from 3.68 to 1.33 X 10(-6) g/ml and increased the calculated maximal response by 15.3%. Thus 13-nle-motilin caused potentiation of the acetylcholine response. Since 13-nle-motilin induced increase of endogenous acetylcholine levels could be excluded, a direct action of motilin on or in the smooth muscle cell is suggested. The results are compatible with the view that in vivo subthreshold doses of motilin may affect cholinergic driven pyloric motor activity.


Release of motilin in man.

Release of motilin in man. The effects on motilin release of various stimuli including an ordinary hospital lunch and ingestion of equicaloric amounts of protein (steamed cod), fat (double cream), or carbohydrate (glucose solution), and intraduodenal instillation of acid (0.1M HCl) and alkali (0.3M tris buffer, pH 10.2) have been investigated in healthy volunteers. Duodenal acidification resulted in a 90% rise of plasma motilin while after intraduodenal instillation of alkali motilin fell. No significant change was seen after a normal hospital lunch and the protein meal, and a small fall was observed after glucose. By contrast, after ingestion of 60 g fat motilin showed a peak increase of 65% at 30 minutes and was still significantly elevated at 60 minutes. Exogenous motilin has been reported to delay gastric emptying and this is also seen after duodenal acidification and fat ingestion. We conclude that motilin may be released physiologically by these stimuli and mediate their effects on gastric emptying in man.


Motilin effects on gastrointestinal motility and lower esophageal sphincter (LES) pressure in dogs. Natural porcine motilin induces phasic contractions of the lower esophageal sphincter in dogs. These contractions are related to gastric contractions, which have the characteristics of interdigestive-motility patterns. Duodenal alkalinization produces an insignificant LES pressure increase after 5 minutes. No effect of motilin was observed when using isolated canine muscle strips.


Intravenous 13-Nle-motilin increases the human lower esophageal sphincter pressure. To elucidate whether, in principle, motilin could serve a role in LESP regulation, the effects of 13-norleucine-motilin (13-nle-m)-synthetic analogue of motilin and biologically just as active as the natural polypeptide-on LESP were investigated in normal subjects. LESP was monitored with the continual withdrawal method. Sets of tests: (1) i.v. pulse doses of 13-nle-m (0.05, 0.1, 0.2, and 0.4 mug/kg) were given to 6 subjects in random order on different days, (2) i.v. bolus injections of 0.6 mug/kg pentagastrin were given to elicit maximal LES contractions, (3) i.v. infusions of 13-nle-m (0.1, 0.2, and 0.4 mug/kg-h; doses doubling every 30 min) were used in 7 individuals, and (4) the effect of atropine infusion of 13-nle-m-stimulated LESP was studied in 6 subjects. (1) Graded i.v. pulse doses of 13-nle-m caused LESP to increase dose-dependently with maximum pressures exceeding basal levels by about 160% (p less than 0.01). After each bolus injection, peak values were achieved within 1-2 min followed by a steady decrease in LESP. (2) Maximum response to 0.4 mug/kg 13-nle-m was about 65% of that to 0.6 mug/kg pentagastrin. (3) i.v. infusions of varying doses of 13-nle-m caused a significant and dose-dependent increase in average LESP. (4) The stimulating effect of an i.v. pulse dose of 0.1 mug/kg 13-nle-m on LESP could be suppressed by concomitant atropine. the human LES is responsive, indeed, to exogenous motilin.


Effect of 13-Nle-motilin on small intestinal transit time in healthy subjects. In 6 female subjects without gastrointestinal diseases, 13-norleucine motilin (13-Nle-M) synthetic and biological analogue of the duodenal polypeptide, motilin, caused acceleration of intestinal transit time. Intravenous infusion of 0.4 mug/kg-h of 13-Nle-M reduced mean transit time by 50 percent. No side effects occurred during infusion of the polypeptide. Radiographic appearance of small intestinal peristalsis and mucosal relief was not influenced by 13-Nle-M.


Vagal influences on gastric acid secretion. Experimental studies in cats.


Motilin-induced mechanical activity in the canine alimentary tract. Gastrointestinal contractile activity from the lower esophageal sphincter to the terminal ileum in the conscious dogs was continuously recorded on a multi-channel polygraph for several weeks by means of chronically implanted strain gage force transducers. It was found that the 24-hour gastrointestinal motor activity consisted of the two different major patterns; the digestive and interdigestive patterns. The interdigestive motor activity was characterized by a cyclic recurring, caudad-moving band of strong contractions interrupted by long lasting motor quiescence. When one band of strong contractions reached the distal ileum, another developed in the LES, stomach and duodenum again and propagated in a caudad-direction. Such recycling episodes repeatedly occurred until the next meal. After ingestion of food, gastrointestinal motor activity was continous and such characteristic interdigestive patterns were not observed. Synthetic motilin, 0.1-2.7 mug/kg/hr, was assayed for its motor stimulating activity in the both states. In the digestive state, an i.v. infusion of motlin had no influence upon the motor activity even if the dose was increased up to 6.0 mug/kg/hr. On the other hand, when motilin was infused during the interdigestive state, it induced a pattern precisely like the naturally-occurring interdigestive contractions. Not only the naturally-occurring contractions but also motilin-induced contractions were strongly inhibited by the ingestion of food or an i.v. infusion of pentagastrin (0.2-1.8 mug/kg/hr). Duodenal acidification (0.1 N HC1, 3-16 ml/kg/hr) in the interdigestive state disturbed or inhibited the regular cycle of the natural contractions but was counteracted by exogenous i.v. infusion of motilin. These findings strongly suggest the view that the interdigestive gastrointestinal motor activity is at least in part regulated by circulating motilin concentration in the blood, however, its cyclic recurring, caudad propagating mechanism may be controlled in part by the nervous system. Motilin is the only substance known to be active during the interdigestive state and therefore may be called the interdigestive hormone.


Doctors to the dying.

Doctors to the dying.


Indications for bone scanning.

Indications for bone scanning.


Nine year old girl with swelling on joints for four months: clinical conference.


Recombinant DNA research: beyond the NIH guidelines.


Meningitis caused by Rhodotorula.

Meningitis caused by Rhodotorula. A case of rhodotorula meningitis in a 21 year old male compromised with acute lymphoblastic leukemia is reported. The yeast was identified as Rhodotorula rubra (Demme) Lodder.


Clinical examination of bone marrow.

Clinical examination of bone marrow.


Further observations on canine spirocercosis in Kenya. The close association of the parasite Spirocerca lupi with oesophageal sarcomas suggests aetiological involvement of S lupi. Further investigations may yield results of significance with respect to comparative oncology. This paper records detailed observations made over an 11 year period, on the incidence and pathological variations of S lupi infections in Kenya.


Critical closing pressure or yield shear stress as the cause of disturbed peripheral circulation? Rheological obstruction is possible on the basis of the known physical properties of blood. The angioarchitectonic arrangement of the mammalian microvasculature makes it especially susceptible to rheological obstruction. This is a price to be paid for the high efficacy and minituarisation which ameliorates the function under physiological conditions. Whenever blood looses its unique fluidity and assumes quasi conventional flow properties of a suspension, obstruction of the microvessels occurs: 1) when the blood perfuses vessels of the appropriate design under pressure insufficient to desaggregate, or deform the cells, or 2) when abnormal interaction between blood cells and cell wall occurs. In these respects, organ-specific differences also have to be taken into consideration; organs in which there are many venules are more susceptible than those with long capillaries: this facts will certainly have to be taken into account when discussing differences between skin and muscle perfusion.


Vibration-induced changes in vascular tone. Longitudinal mechanical vibrations in sonic range (10-100 Hz) and of moderate amplitude (50-500) considerably reduce the contractile force of smooth muscle as well as striated muscle. Experiments elucidating the mechanism behind this effect are described. The inhibition of the contractile force is probably due to a direct interference with the action of the contractile proteins. Vibrations are supposed to increase the rate with which the interfilamentary crosslinks are broken. Thereby the number of established crosslinks is reduced and thus the force. Finally a hypothesis concerning the possible role fo this phenomenon in the pathogenesis of vibration induced Raynaud syndrome is forwarded.


Raynaud's phenomenon of occupational origin. An epidemiological survey.


Raynaud phenomenon in obliterative arterial disease on the upper extremity.


Vibration induced changes of sympathetic vasomotor tone.


Finger blood flow in healthy subjects of different age and sex and in patients with primary Raynaud's disease. Finger blood flow measured at rest and after 3 minutes of circulatory arrest by strain gauge venous occlusion plethysmography was significantly higher (p less than 0.001) in a group of 13 healthy young men than in a group of 12 healthy young women. The flow values in 13 women in the meopause reached almost the level found in men. Hormonal factors might explain these differences. Between the group of the healthy young women and the 12 patients with Raynaud's disease there were only gradual differences in finger blood flow. Peak flow after 3 minutes of circulatory arrest was significantly lower in the patients (p less than 0.05). Whereas flow at rest showed only a tendency to lower values (mean room temperature 24 degrees C). The spontaneous and cold induced vasopastic attacks characterized by a decrease in finger volume and by very low or not measurable finger flow.


Vasospastic symptoms in neurological disorders.


Methods for the evaluation of peripheral vascular function in the upper extremities.


Primary and secondary Raynaud phenomena.


Application of time derivative curves in the evaluation of time dependent physiological functions.


Detection of occlusive arterial disease in the hand in patients with Raynaud's phenomenon.


Fluorescein angiography especially of the upper extremities. The technique used in sequential fluorescein angiography of the upper extremities is described. The sensitivity and reproducibility of the method are exemplified and discussed in regard to its applicability in diagnosis of organic arterial obliterations, e.g. in Raynaud's phenomenon as well as to its usefulness in evaluation of reconstructive arterial surgery and medical treatment with respectively thrombolytic (Brinase, Astra) and microhaemorheologic agents (Venoruton, Zyma; Arwin, Knoll) or those with an influence on systemic haemodynamic factors as in induced hypertension. The importance of standardized experimental conditions is emphasized, particularly with reference to vasodilatation. The method represents a new possibility of obtaining clinically a functional over-all information on the nutritional blood flow of rather extensive skin areas. Also, it can illustrate the interaction between macro- and microcirculation. Segmental macrovascular occlusions without concomitant damage of the corresponding terminal vascular area mainly cause a prolongation of the fluorescence appearance time. Obstruction of the microvascular blood flow reveals itself as more definite changes in the fluorescence pattern of the affected skin areas.


Velocity of red blood cells in human nailfold capillaries.


Vascular compression syndromes of the upper extremity.


Stenosing arteritis of the subclavian-axillary arteries (polymyalgia rheumatica sive arteritica). According to recent investigations a stenosing arteritis of the subclavian-axillary arteries almost always is only one localization and an extreme variant of a systemic vascular disease, affecting aorta and large arteries, by pathologists called giant-cell arteritis or non-syphilitic aortitis and arteritis. The clinical manifestation of this disease process is often limited to a "painful shoulder syndrome".


Treatment of patients with secondary Raynaud's syndrome. Treatment of secondary Raynaud's disease must be a treatment of the impaired microcirculation in the ischemic tissue. It can be performed in 3 ways: 1) By treating the vasospastic component 2) By reconstruction of occlusions or stenosis in the greater arteries 3) By improvement of the flow properties of blood. While the first two types of treatment often give unsatisfactory results, a new rheological therapy using Ancrod seems to be successful. This drug, a purified fraction from a snake venom lowers the fibrinogen concentration in blood therapy improving the flow properties of blood and plasma. In 5 patients suffering from severe secondary Raynaud's disease Ancrod was injected subcutaneously for a 2-4 week period. Some days after starting the treatment, the ischemic pain was reduced and finally disappeared. The beneficial effect continued even after ending the treatment. The mode of action of this new drug has been discussed.


Effect of nicotine on isolated human blood vessels. The action of nicotine was studied in isolated human vascular strip preparations using isometric recording of tension. Nicotine per se did not elicit any significant changes of smooth muscle tone. The effect of noradrenaline and direct smooth muscle stimulation, however, was enhanced. This action presumably is not dependent upon an adrenergic nervous mechanism, as in the intact organism but seems to be dependent upon a direct smooth muscle stimulation in itself not sufficiently strong to induce a contraction but leading to facilitated stimulation and propagation of the response.


Thrombosis of the subclavian vein--a feature of the thoracic outlet syndrome.


The influence of the internal compliance of a respirator on the alveolar gas distribution. The occurrence of intrapulmonary redistribution "pendelluft" during the plateau phase of a respirator, with and without internal compliance, was studied in a lung-model which simulated an obstructive inhomogeneity. Internal compliance was achieved by adding a flask, with a variable volume, to the patient circuit of a respirator which had a low compressible volume (Engström Care System ECS 2000, Junger Instrument AB, Sweden). The amount of redistributed volume was found to be dependent upon the internal compliance. Without additional compressible volume, the ventilator produced up to 18% redistribution which under all conditions could be brought below the 1% level when an internal compliance was introduced. A highly significant correlation between the amount of redistributed volume (pendelluft) and the discharge time-constant of the plateau (taupl = CI (RI + Rtr) could be established. The results of mathematical consideration gained from an electrical analogue coincided with our experimental findings. From this, some consequences could be derived for the design of an internal compliance for use with a respirator.


The ferruginous body content of lungs at autopsy in Boston 1928-1932.


Shortening of labour especially the period of dilatation with low frequency vibrations against cervix uteri. A clinical study.


Fibroxanthosarcoma of the uterine cervix: cytopathologic and histopathologic manifestations. A case of fibroxanthosarcoma of the uterine cervix is reported with its cytopathologic manifestations. The cellular features of two cell populations characterized by atypical cells of fibroblastic and histiocytic types, suggests the correct diagnosis. The possibility of uterine sarcoma must be considered in the differential diagnosis of bizarre and unusual cytologic findings.


Fetal mortality and morbidity following breech delivery.


The role of cytology in the detection of malignant lymphoma of the uterine cervix. The success of cytologic examination in the diagnosis of malignant lymphoma of the cervix is at present limited. The generally accepted cytologic criteria for the identification of malignant lymphoma may have to be applied with caution when examining material obtained by abrasive technique; the diagnosis should not be entirely excluded, even in the presence of cell aggregates.


Changes in cortical responsivity to multisensorial stimuli during exposure to urban traffic noise.


Temporary threshold shift (TTS) due to exposure to urban traffic noise.


Changes in stapedius reflex amplitude and latency following exposure to urban traffic noise.


Changes in the time of reaction to light and sound signals in the presence of urban traffic noise.


Condylomatous lesions of the cervix and vagina. I. Cytologic patterns. Condylomatous lesions, although readily diagnosed on the vulva, are often missed in the vagina and on the cervix by clinical examination alone. The lesions are, however, quite common and may be misdiagnosed as mild dysplasia by cytology, colposcopy and even tissue examination. Condylomatous lesions are presently diagnosed on cytologic evidence in nearly two per cent of asymptomatic patients screened in our program and followed-up by colposcopy and tissue examination, when indicated. The cytologic presentation of these lesions is quite characteristic. The main features are seen in squamous cells: enlargement, bi- or multinucleation, hyperchromasia, peri-nuclear clearing, amphophilia and dyskeratotic changes. Our present experience indicates that a large number of lesions previously classed as mild dysplasias actually represent various stages of condylomatous lesions. When these stages of viral changes are removed from the group of dysplasias, the remaining cases become of much greater significance as the early stages of evolution of carcinomata of the cervix.


Behaviour of CNV during exposure to urban traffic noise.


Sputum cytology of metastatic carcinoma of the lung. The cytopathology of 47 cases of metastatic carcinoma of the lung and of 28 cases of recurrent or metastatic bronchogenic carcinoma is reviewed. The diagnostic yield was better for recurrent than for metastatic carcinoma but overall was comparable to that of primary bronchogenic carcinomas. The metastatic tumors were located in all areas of the lung and included single as well as multiple lesions. The positive yield did not differ significantly in relation to any of the pathologic features but was somewhat higher if the metastases were large and centrally located. A definite differentiation of the metastatic tumors, usually adenocarcinomas, from new primary bronchogenic carcinomas is often possible particularly if the cytopathology can be compared with that of the primary lesion. Specific cytologic features include the relative lack of cohesion and the formation of columns in metastatic breast carcinomas, the formation of larger cohesive well circumscribed nodules composed of tall columnar cells in metastatic colon carcinomas, clear cell features in some metastatic adenocarcinomas of the kidney, and the small cell size and uniform, regular nuclear features in the often cytologically well differentiated metastatic carcinomas of the prostate.


The value of rapid imprint smears in the surgery of skin cancer.


EEG changes induced by exposure to urban traffic noise and while noise.


Effects of urban traffic noise in relation to basic personality.


Measurement of phonatory level in the presence of urban traffic noise.


Intelligibility of spoken words in the presence of urban traffic noise.


Morphology and DNA content of endometrial cancer nuclei under progestogen treatment. Twelve endometrial cancers have been observed before and during progestogen treatment. Eight were well-differentiated and displayed an objective response. It was essentially characterized by a volumetric reduction of the nucleus and the disappearance of tetraploid nuclei. The DNA content remained diploid or near-diploid. Reduction of nuclear non DNA proteins under hormonal treatment is suggested. Morphology and deoxyribonucleic acid (DNA) content of endometrial cancer nuclei under progestogen treatment are reported.  12 endometrial cancers were observed before and during treatment.  8 were well-differentiated and displayed on objective response.  The response was characterized by a volumetric reduction of the nucleus and the disappearance of tetraploid nuclei.  DNA content remained diploid or near-diploid.  Reduction of nuclear non-DNA proteins in endometrial cancers under progestogen treatment is suggested.


Research on phoneme emission in relation to urban traffic noise.


Urban traffic noise: auditory and extra-auditory effects. Introduction, bibliographical survey, research aims and technical notes.


Monolayer cell cultures as target cells for the study of lymphocyte cytotoxicity in cancer patients. Lymphocytotoxicity using S3-Hela target cells has been studied in 20 cancer patients treated with ionizing radiation (head and neck, lung and breast cancers). Monolayer cultures of Hela cells were marked with radioactive 51 Chromium and cultured with non stimulated or phytohemagglutinin (PHA) stimulated lymphocytes. This study shows a spontaneous decrease of lymphocytotoxicity in cancer patients as compared with normal subjects and an immunodepressive effect of radiotherapy. We observe a significant decrease of lymphocytotoxicity for either stimulated or non-stimulated lymphocytes at the end of radiation treatment. Moreover one month after completion of radiotherapy a possible repair of a lymphocytoxicity seems to be related with a short-term (6 months) good prognosis.


Urban traffic noise, cardiocirculatory activity and coronary risk factors.


Urban traffic noise: auditory and extra-auditory effects. Concluding remarks.


Characterization of mononuclear phagocytes in human CSF using membrane markers. The purpose of this investigation was to demonstrate those membrane receptor sites on mononuclear phagocytes of human CSF which provide additional evidence for their monocytic origin and function. Using a heterologous system, sheep red blood cells were coated with IgG- and IgM-fraction of the anti-Forssman-antiserum of rabbits. In another series of experiments, sheep red blood cells were additionally sensitized with fresh human serum as a source of complement. The possible inhibitory effect of human IgG on the uptake of red cell antibody complexes was tested. Washed and pretreated sheep red cells were added to different fresh CSF specimens from patients, whose CSF exhibited no conspicious biochemical, serologic or cytologic alterations. The percentage of phagocytizing mononuclear phagocytes was evaluated. When the particular IgG EA reagent described was utilized, most of the mononuclear phagocytes consistently exhibited the IgG- and complement-receptor activity which selectively characterizes blood monocytes and related cells.


An autopsy case of type II glycogenosis. An autopsy case of Type II glycogenosis was reported with detailed description of ultrastructural findings. In addition to two typical patterns of glycogen deposition, membrane-bound lysosomal glycogen and membrane-free cytoplasmic glycogen, we observed numerous vacuolar structures in liver cells and a large deposition of nomogeneous materials between fragmented myocardial fibrils. These findings were briefly discussed in this manuscript.


Relation between cell composition of pleural effusions in patients with pulmonary carcinomas and their clinical courses. 1) Cancer cells of the effusions were decreased by chemotherapy, but this did not always indicate a good clinical course. 2) When the clinical condition was fairly good, the percentage of lymphocytes predominated in the pleural effusion. 3) When the clinical conditions became rather critical, there was an increase in the number of macrophage. 4) The cytologic findings were observed prior to the time the clinical symptoms became manifest. 5) The percentage of lymphocytes and macrophages in pleural effusions was not related to the percentage of lymphocytes and monocytes in peripheral blood.


Long-term cytogenetic studies in acute leukemia of children; the nature of relapse. Sequential long-term cytogenetic studies in 71 children with acute leukemia were designed to investigate the nature of relapse after prolonged remission. In the overwhelming majority of the cases the findings suggested clonal identity of the leukemic cell population in relapse with that studied at the onset of the disease, notwithstanding considerable karyotypic instability in almost half of the patients. In a small minority an independent origin of the relapse clone could not be excluded on cytogenetic grounds but was considered unlikely, since mechanisms capable of accounting for the changes observed in these patients could be demonstrated in other cases. The persistence of diploid leukemic cells in the presence of an aneuploid subclone was demonstrated in the relapse bone marrow and/or spinal fluid in all active phases of the disease. On this basis the conversion from an aneuploid to a predominantly or exclusively diploid karyotype could be visualized, and a new model of clonal evolution, involving repetitive formation of abnormal karyotypes from a surviving diploid clone could be suggested.


The numerical composition of cellular samples from the female reproductive tract. III. Cases with mild and moderate dysplasia of uterine cervix.


IMFRA (intermittent intrathecal methotrexate and fractional radiation) plus chemotherapy in childhood leukemia. A protocol for the prophylaxis of CNS leukemia was devised involving intermittent low-dosage radiation of the craniospinal axis combined with single intrathecal injections of MTX. The retionale for this protocol was the timing of first CNS relapses in patients not receiving prophylaxis which suggests that leukemic colonization of the CNS is not restricted to the initial stage of the disease and that periodic measures might be advantageous. The low dosage of radiation was chosen because it is well tolerated and has been found temporaily effective in overt CNS relapse. The two series of patients were comparable as to various parameters. Results after three years of observation were comparable to those obtained by other with a single initial course of high-dose radiation, with an expected 50% uninterrupted complete 5-year remission. On the basis of 30 months follow up in 26 patients, the therapy is well tolerated. An increase in morbidity due to infections in remission was not associated with a higher mortality.


Chemotherapy of acute lymphoblastic leukemia in children. Between 1969-1973, 75 consecutive children under the age of 15 years with acute lymphoblastic leukemia were treated with a multiple-drug regimen (L-2). Prophylaxis for meningeal leukemia was limited to the repeated intrathecal injections of methotrexate. Seventy-four patients achieved remission; the duration of remissions could be evaluated only for 70. Relapse terminated complete remission within 1-54 months in 21 children. Four of these relapses were confined to the central nervous system. Forty-nine patients continue in complete remission from 23 to 63 months. Chemotherapy has been discontinued in 29 children, and 25 of these remain without evidence of recurrence for 2-27 months posttreatment.


Bilateral interstitial pneumonia in acute lymphoblastic leukemia. Of 148 children with acute lymphoblastic leukemia (ALL) 34 had bilateral interstitial pneumonia (BIP). Their records were reviewed retrospectively to evaluate the incidence of this pneumonia and delineate the various etiologic factors involved. All but 1 were in remission; 82% of the episodes occurred within the first 6 months, the majority of these occurring during the first 3 months of diagnosis of ALL; 16 were receiving methotrexate (MTX), and 14 were receiving combination chemotherapy with vincristine, prednisone and 6-mercaptopurine (6-Mp) and 4 were on no systemic therapy. Thirty patients with 35 episodes recovered within an average period of 18 days, including clearance of radiologic findings; 4 died. Four had open lung biopsies without complications. There was a single case of pneumocystis carinii infection diagnosed postmortem. Laboratory data and histopathologic findings (of 4 biopsies and 3 remaining autopsies) were suggestive of a viral etiology. The incidence of BIP in ALL at Children's Hospital of Michigan is 22.9% with a mortality rate of 10.3%. The incidence of pneumocystis carinii infection appeared to be low. Hypersensitivity to MTX was not substantiated.


Terminal candor and the coda syndrome.

Terminal candor and the coda syndrome.


The human spleen as revealed by scanning electron microscopy. The three-dimensional world of the spleen was explored by scanning electron microscopy on both arterially perfused and nonperfused specimens, as well as on plastic corrosion casts of splenic vasculatures. Of 25 spleens studied, 18 were examples of hypersplenism. These were contrasted to 7 essentially normal spleens taken from children being staged for treatment of Hodgkin's disease whose spleens proved to be uninvolved in the pathologic process. Splenic sinuses in all 25 spleens were typified by a degree of porosity. RBC were caught in the act of entering sinuses from splenic cords. These sinus windows thus represent one end of an "open" circulation pathway. In casts of microvasculature, direct arteriovenous connections were demonstrated, thus establishing an anatomical basis for an often disputed "closed" circulation pathway. Spleens from 7 patients with hereditary spherocytosis had a super abundance of red pulp. Splenic cords were thickened and crowded with spherocytes, many of which presented slightly wrinkled membranes, as were also noted on the peripheral blood RBC. It is possible that these membrane features are unique for HS and reflect the intrinsic membrane abnormality in protein composition. The 7 spleens from chronic idiopathic thrombocytopenic purpura had white pulp as the predominant region. Germinal centers were frequent. Lymphocytes and plasma cells with well-developed microvilli were suggestive that release of antiplatelet antibody might be occurring in white pulp. Platelets were especially notable in peripheral white pulp and marginal zones. Platelet clumps were observed, generally adjacent to spleenic macrophages.


The deviated midline.

The deviated midline.


The influence of transseptal fibers on incisor position and diastema formation. Transseptal fibers are a part of the gingival group of fibers of the periodontal membrane, and they are very tough and resistant. They form a chain from tooth to tooth which, provided that it remains intact and is sufficiently strong to resist displacing muscular pressures, will preserve the contacts between the teeth throughout the arch. If the continuity of the chain is interrupted, the balance of the forces acting upon the teeth on either side of the break is upset and considerable displacements can occur. Maxillary median diastemas are classified as "simple" or "persistent" according to their etiology, and an operation to clear the upper midline suture of transeptal fibers is described as an essential part of the treatment of persistent upper median diastema.


Superior repositioning of the maxilla: stability and soft tissue osseous relations. The skeletal stability and soft-tissue changes associated with superior repositioning of the maxilla by Le Fort I osteotomy or simultaneous anterior and posterior maxillary osteotomies was studied in thirty patients by means of a computerized craniofacial model. Excellent skeletal stability was demonstrated 14 months postoperatively. Postsurgically, the reduction in lower face height and amount of maxillary incisor exposure resulted in improved facial balance. The use of a computerized osseous and soft-tissue craniofacial model has added a new dimension to evaluation of surgical changes associated with correction of dentofacial and craniofacial deformities.


The reliability of head film measurements. 3. Tracing superimposition. The superimposition of tracings from lateral skull x-ray films taken at different timepoints is an important method for assessing developmental and treatment changes through time. The usefulness of the data derived is, however, limited by the fact that the physical act of superimposing tracings is performed with some error. The magnitudes of error for superimpositions on different "planes" have not been amenable to quantitation by previously available methods. Using newly developed computer-aided techniques, we have been able to quantitate both the primary errors of tracing superimposition and the associated secondary landmark displacements for four conventionally employed anatomic reference "planes". For each reference "plane," twenty-five independent film pairs were examined independently by each of four judges. Therefore, 100 acts of tracing superimposition were available for each reference "plane." Output data are presented which appear to support the conclusion that measurement errors in tracing superimposition are a consequential factor affecting the confidence which should be placed in head film comparisons, particularly with regard to individual cases. Some consequences of this conclusion with respect to growth prediction and to the evaluation of treatment effects are considered.


A biometric study of orthopedically directed treatment of class II malocclusion.


Inherent cellular radiosensitivity of human tumors of varying clinical curability. It is well known that radiation therapy can be successfully used to cure or control some types of human tumors, while consistently failing in others. This has been ascribed to several factors including differences in the intrinsic sensitivity of the tumor cells and in their ability to recover from radiation damage. In this study, human tumor cells from an osteogenic sarcoma, a glioblastoma, and two medulloblastomas, as well as cells from human skin, were established in tissue culture, and the in vitrox x-ray survival and DNA repair parameters determined. No significant differences in either clonogenic survival or DNA strand rejoining ability could be detected among these human tumors or skin cells, despite the wide variability in their radiocurability in vivo. In addition, skin cell strains derived from patients exhibiting markedly sensitive or resistant skin reactions during fractionated radiotherapy showed no differences in survival characteristics from normal controls. It is therefore suggested that the wide range of radiocurabilities seen among various human tumors cannot be explained on the basis of inherent cellular factors responsible for the survival of tumor cells after x-irradiation.


Inhalation of benzpyrene and cancer in man.


Occupational aspects of scrotal cancer and epithelioma.


Cancer experience among coke by-product workers. This paper presents the site-specific cancer mortality, 1953-1966, for men employed in by-product coke plants in Allegheny County, Pa. Approximate relative risks, which take into account race, age, and calendar years of follow-up, have been calculated for various work areas of the coke plant. The major findings are: 1. As indicated previously by Lloyd and Redmond, men with five or more years at the coke ovens have an excess risk of dying from lung cancer and kidney cancer. 2. Cancers of the digestive system are significantly elevated in nonoven workers. Cancers of two sites, the colon and pancreas, account for the total excess in cancers of the digestive system. 3. Cancers of the buccal cavity and pharynx appear high in nonoven workers, although the number of deaths involved is small. These observations clearly indicate the need to consider nonoven as well as oven workers when evaluating cancer hazards in the coke plant.


Multiple factors in carcinogenesis.

Multiple factors in carcinogenesis.


Leukemia associated with benzene exposure.


Cancer mortality among rubber workers: an epidemiologic study. Several previous epidemiologic studies of the rubber industry--an industry that uses many chemicals--have identified excess mortality from certain specific cancers. In this study, four cohorts of active and retired workers, at four major rubber-tire plants, were identified historically and followed for the ten-year period from 1964 to 1973. The cancer mortality of these four population was compared, separately and combined, with that of the general community. For all cancers combined, there was a slight excess above the expected number of deaths, whereas for some specific cancers (stomach, colon, prostate, and neoplasms of the lymphatic and hematopoietic system) there was a marked excess of deaths. Proportional mortality analysis at other small plants revealed similar excesses for these cancers, and some excess for lung, bladder, and CNS cancers. Analysis of detailed individual work histories reveals an association of certain cancers with specific job exposures; in particular, lymphatic leukemia and solvent exposure, and lung cancer and curing-room exposure. For both bladder cancer and stomach cancer, preliminary analyses indicate an association with groups of jobs in adjacent production stages (handling and mixing raw ingredients, and processing the "green" precured rubber, respectively). Further analytic studies are currently under way to identify groups of rubber workers at increased risk of other specific cancers.


Recent approaches to the control of carcinogenic exposures. Case study 2: Benzidine and 2-naphthylamine - voluntary substitution or technological alternatives.


Case study 1: asbestos--the TLV approach. A review of the control of carcinogenic exposures using the TLV approach presents a prospect of limited effectiveness. With asbestos, as with any carcinogen, no threshold is known below which no health effect may be manifest. At best, we have only limited dose-response information at levels much above those of practical concern. In the case of asbestos, current exposures can only be described crudely at any level of exposure, and health effects are only known for past high, but ill-defined, exposures. Limited information exists on the effects of synergistic interactions with other materials. The current U.S. TLV, based on data concerned with occurrence of asbestosis, has not been evaluated with regard to possible effectiveness in the prevention of asbestos cancer. Yet cancer is the heart of the asbestos-hazard problem. Finally, enforcement of the existing TLV, especially for asbestos has been limited, frequently absent, and often ineffective. Workers are exposed in many situations to levels much above the current standard. As discouraging as this picture may seem, a TLV can be useful for stimulating the development and application of engineering-control procedures. The application of these procedures, however, must be specified and mandated in future standards to lower worker exposures to the minimum commensurate with existing technology. As technology is developed that makes lower exposure levels possible in a large part of the industry, TLVs should be reduced to take advantage of that technology.


Recent approaches to the control of carcinogenic exposures. Case study 3: vinyl chloride--best available technology.


Inorganic arsenic--ambient level approach to the control of occupational cancerigenic exposures. In 1820 the first malignancies ascribed as due to occupational arsenic exposure were reported as scrotal cancers among smelters. A century later the causal relationship between chronic occupational, environmental or medical arsenical exposure and skin carcinogenesis was firmly established. From 1948 to 1975, nine out of eleven epidemiological studies have shown, initially or upon review, significant excess mortality from respiratory cancer among diverse occupations exposed to various inorganic arsenicals. Two of the nine studies have shown concommitant, significant excess mortality from lymphatic cancer, and another, from skin cancer. Additionally, two such studies have revealed a dose-response relationship between arsenical exposure and lung carcinogenesis. In the first, reported in 1969, the relationship was semi-quantitative, with a possible interactive role by sulfur dioxide or other contaminants. The other demonstrated a dose-response which was quantitative for arsenic per se. Upon our reinterpretation, this dose-response also demonstrated an increased lung cancer mortality risk apparently at arsenic concentrations above 1 mug/M3, calculated as the 8-hour TWA daily exposure over a 40-year working life. However, these and related data do not reveal a definite no-effect exposure level. Thus, in the absence of data documenting a cancerigenically safe level of occupational exposure and because of the environmental ubiquity of arsenic, the conclusion is drawn that the arsenic body burden of workers should not be occupationally increased above that produced by the ambient level.


Occupational carcinogenesis. Toward an integrated program of government action.


Humidity output of the Columbia pediatric circle.


Guidelines for a NIOSH policy on occupational carcinogenesis.


Prevention of occupational cancer--toward an integrated program of governmental action: role of the National Cancer Institute.


Modification of a Bird Mark-14 anesthesia ventilator for greater versatility.


Prevention of occupational cancer--toward an integrated program of governmental action.


The federal role in prevention of occupational cancer in mines and mills.


Carcinogenesis. Dose-response relationship and threshold concepts.


Sputum cytology among aluminum potroom workers.


Governmental action in Britain.

Governmental action in Britain.


Cancer mortality in the steel industry.

Cancer mortality in the steel industry.


Cancer mortality pattern associated with exposure to metals.


Cancer mortality patterns in the lead industry. The mortality of 7,032 men employed for one or more years in lead production facilities ("smelters") or battery plants was observed over a 23-year period, 1947-1970. There were 1,267 certified deaths. Lead absorption in many members of the cohort was known to have been greatly in excess of accepted standards. The standardized mortality ratio (SMR) for all causes was 107 for smelter workers and 99 for battery plant workers. Deaths from malignant neoplasms were somewhat elevated in both groups, the SMR being 133 for smelter workers and 111 for battery plants. The excesses arose largely from tumors of the digestive organs and the respiratory system. Only three deaths are attributed to malignant renal tumors and seven to tumors of the central nervous system. The latter findings were of interest in view of the experimental production of renal tumors in rats and mice by the injection or oral administration of very large doses of lead salts, and the report by one group of investigators of gliomas in rats fed lead subacetate. Studies are continuing to characterize more fully the exposure of the above lead workers to substances other than lead. Additional follow-up of the cohort is also contemplated.


An anesthetic gas scavenger for the Jackson-Rees system.


Metal-material workers and lung cancer in Japan. The distribution by occupation of 39,255 lung cancer deaths in eight years, from 1960 to 1967, was analyzed. An age-standardized comparison of actual deaths and expected deaths revealed that cancer of the lung had tendency to occur with a significantly higher frequency in (1) metal material workers (Obs., 232; Exp., 176.5), and (2) workers in mining and quarrying occupations (Obs., 151; Exp., 127.9). By similar analysis, farmers, miners, and metal-material workers were noted as high-risk occupations for stomach cancer and clerical workers, and farmers were noted as such for leukemia. The value of occupational cancer in monitoring by such a simple analysis was stressed (see Figure 1).


Cancer mortality among cadmium production workers.


Advantages of infant ventilators over adapted adult ventilators in pediatrics. A lung simulator with variable compliance and resistance components was used to evaluate the dynamic compliance of the Bournes, Babybird, and Pediatric Emerson postoperative ventilators. With increase in airway pressure from combined changes in compliance and resistance, the internal compliance of the Bournes was lowest and the internal compliance of the Emerson was highest. With low constant airway resistance (50 cm/L/sec), the Babybird exhibited tidal volume losses similar to those of the Bournes in the face of decreased lung compliance. With constant lung compliance (10 ml/cm H2O) and increasing airway resistance, the Babybird had marked volume losses at higher volumes. Under all simulated conditions, internal compliance of the Emerson, although large, was relatively constant and the Bournes had the smallest internal compliance.


Respiratory disease mortality among uranium miners. A mortality analysis of a group of white and Indian uranium miners was done by a life-table method. A significant excess of respiratory cancer among both whites and Indians was found. Nonmalignant respiratory disease deaths among the whites are approaching cancer in importance as a cause of death, probably as a result of diffuse parenchymal radiation damage. Exposure-response curves for nonsmokers are linear for both respiratory cancer and "other respiratory disease." Cigaret smoking elevates and distorts that curve. Light cigaret smokers appear to be most vulnerable to lung parenchymal damage. The predominant histologic cancer among nonsmokers is small-cell undifferntiated, just as it is among cigaret smokers.


Neoplasia in the wood and pulp industry.


Laboratory approaches to the identification of carcinogens.


Oral and pharyngeal cancer in textile workers.


Occupational asbestos exposure, smoking, and laryngeal carcinoma.


Household-contact asbestos neoplastic risk.


Mortality patterns among fibrous glass production workers.


Mortality patterns among hard rock gold miners exposed to an asbestiform mineral.


Discussion paper: asbestos fiber exposures in a hard rock gold mine.


Occupational carcinogenesis. High-risk industrial groups: identification, education, and surveillance. Tyler Asbestos Workers Program. It is concluded that sputum cytopathology is an excellent, simple, noninvasive, painless, and inexpensive means for early detection of malignant and premalignant lesions of the lung, and that no special techniques are necessary for the identification of ferruginous bodies.


Geographic patterns of cancer risk: a means for identifying possible occupational factors.


Cytological monitoring of nickel sinter plant workers.


Early indices of cancer risk among uranium miners with reference to modifying factors.


Hospital admission records: a source for identifying occupational groups at risk of cancer.


Methodologies for risk assessment in occupational carcinogenesis.


The IARC program on the evaluation of the carcinogenic risk of chemicals to man. The International Agency for Research on Cancer has initiated a program to evaluate the carcinogenic risk of chemicals to man. This program is centered on the production of monographs on individual chemicals, consisting of data on use and production, carcinogenicity in experimental animals, epidemiological studies and case reports, and other biological data such as metabolism and mutagenicity, and ending with a balanced evaluation of all the data made by an international group of experts. Chemicals to be surveyed for the preparation of monographs have so far been selected among those for which some evidence or suspicion of carcinogenicity in experimental animals and/or man exists and for which human exposure is known to occur. Of the 196 compounds already evaluated, 17 have been found to be associated with cancer in man. Ninety-four compounds were definitely carcinogenic in experimental animals, and 41 were shown to have a limited carcinogenic effect in experimental animals. A number of the chemicals found to be carcinogenic in experimental animals are produced in very large quantities. The type of exposure to the 17 chemicals found carcinogenic to man was occupational for fourteen, medicinal for two, and dietary for one.


Methodologies of risk assessment.

Methodologies of risk assessment.


Neoplastic risk among workers exposed to vinyl chloride.


Occupational carcinogenesis. A case for worker involvement in risk assessment.


Occupational carcinogenesis. Statistical extrapolation methods for estimating risks from animal data.


Occupational carcinogenesis. Predictive value of carcinogenesis bioassays.


Precursor lesions in exposed populations as indicators of occupational cancer risk.


Lung cancer and mesothelioma during prospective surveillance of 1249 asbestos insulation workers, 1963-1974.


Current concepts of carcinogenesis. Discussion.


Oncogenic and mutagenic risks in communities with polyvinyl chloride production facilities.


Cancer among benzoyl chloride manufacturing workers.


Cancer and congenital anomalies associated with anesthetics.


Cancer risks among workers exposed to chloroprene.


Cytologic observations and cancer incidence following exposure to BCME.


Cancer mortality among workers exposed to cutting-oil mist.


Bacillus Calmette-Guérin contact immunotherapy of local and metastatic deposits of rat tumors. Adjuvant contact therapy with BCG can be used to control tumor deposits at local subcutaneous sites and at other sites, particularly pulmonary metastases and pleural tumor growths. This treatment method is generally quantitatively more effective than general immunostimulation, or active immunotherapy that employs vaccines of adjuvant and tumor cells. Furthermore, this treatment is effective in hosts that lack full immunocompetence, making it still feasible in immunosuppressed patients. The current evidence indicates that local activation of host macrophages is probably the essential effector mechanism of adjuvant contact therapy.


Immunotherapy of cancer patients with Bacillus Calmette-Guérin: summary of four years of experience in Japan. Active immunotherapy with living BCG was conducted on 98 patients with various types of cancer. The candidates for this therapy were patients with residual or inoperable cancer of the colorectum, liver, breast, biliary tract, lung, and other organs with a follow-up of 4-58 months. Eleven of the 98 (11%) were able to survive for as long as 37-58 months (mean survival time 42.5 months) because of this treatment and are still living. Another 11 patients are also alive more than 24 months after starting treatment. Thirty-seven patients, however, succumbed within 12 months despite BCG immunotherapy. On the other hand, 37 patients in the control group, who shared the same clinical status and did not receive BCG therapy during this period, underwent unhappy courses for 2-12 months (mean survival time 8.7 months). The pretreatment immunoresponsiveness of these 98 patients was suppressed, as measured by the following immunologic parameters: T-cell subpopulation in the peripheral blood, stimulation index of PHA, and skin tests to DNCB, KLH, PPD, and PHA. All of these parameters improved shortly after initiation of BCG injections in 22 patients who survived more than 24 months. In contrast, in patients who died within 12 months, immunoresponsiveness remained suppressed throughout the course. This result has suggested that there was an apparent correlation between the effectiveness of BCG and immunoresponsiveness. In addition, a good correlation was observed between the duration of inflammatory reactions at BCG injection sites and clinical prognoses. Moreover, it was shown that a relatively high amount of BCG (20-80 mg as an initial dosage) and repeated injections of living BCG were necessary to obtain a sufficient enhancing effect on the immunocompetency of these late-stage cancer patients. The most conventional criterion used to determine an optimal time for booster injections of BCG was measurement of the PPD-evoked skin reaction at the BCG injection site, that is, Koch's phenomenon. When a marked flare-up reaction of more than 2.5 X 2.5 cm in size was observed, the effect of BCG was considered to be continuing, and no additional booster injection was needed. The mean interval between the first and second BCG injections was 6.2+/-1.1 months in patients who survived more than 2 years. In contrast, the duration of this reaction was only transient in ineffective cases. The most frequent side effects of this therapy were fever and malaise; these complications occurred in 62% of the cases. No severe side effects, such as dissemination, anaphylactic shock, or granulomatous hepatitis, have been experienced throughout this study, even in patients to whom a total dosage of more than 200 mg of living BCG were injected.


Randomized trial of Bacillus Calmette-Guérin (percutaneous administration) as surgical adjuvant immunotherapy for patients with stage-II melanoma.


Discussion paper: treatment of superficial bladder cancer in man.


Immunotherapy of human solid tumors with Bacillus Calmette-Guérin: prolongation of disease-free interval and survival in malignant melanoma, breast, and colorectal cancer.


Discussion paper: effect of hemolytic streptococci on lymphocytic leukemia in AKR mice.


Therapeutic effectiveness of neuraminidase-treated tumor cells as an immunogen in man and experimental animals with leukemia. The immunogenicity of leukemia L1210 in DBA/2 Ha and 6C3HED lymphosarcoma tumor cells in C3H/f mice was significantly increased after treatment with V. cholerae neuraminidase. DBA/2 Ha and C3H/f mice repeatedly immunized with neuraminidase-treated tumor cells rejected subsequent challenge of 10(7) or 10(6) untreated tumor cells, respectively. Based on the 51Cr microcytotoxicity assay, both strains of mice showed strong complement-dependent antibody titers and cell-mediated immunity. Sera and splenic lymphocytes from immunized C3H/f mice neutralized the tumorigenicity of 6C3HED lymphosarcoma and protected the recipient C3H/f mice against the disease. Immune lymphocytes pretreated with anti-theta sera lost their ability to neutralize the tumorigenicity of lymphosarcoma, and they failed to be stimulated by T-cell mitogens. We studied the effectiveness of chemoimmunotherapy in DBA/2 Ha mice with leukemia L1210. A single near optimal dose of BCNU 2 days after implantation of 10(6) tumor cells increased the survival time. A single immunization with 2 X 10(7) neuraminidase-treated L1210 tumor cells 4 days after cytoreductive therapy increased survival and resulted in cures for 50% of  animals. Immunization of mice with neuraminidase-treated tumor cells and MER produced indefinite survival in a larger percentage of mice than did either treatment alone. AKR mice with spontaneous leukemia treated with combination chemotherapy sustained an 180% increase in life-span. Combination chemotherapy plus immunization with neuraminidase-treated syngeneic or allogeneic (Gross virus-induced) E2G leukemia cells were highly effective in prolonging the life-span of the immunized leukemic AKR mice. The experimental data led to clinical trials in acute myelocytic leukemia with neuraminidase-treated a-logeneic myeloblasts. Patients with acute myelocytic leukemia were randomized into two groups after remission induction. The median remission duration of patients on sustaining chemotherapy alone was 19 weeks (8 patients), whereas six of nine patients who received neuraminidase-treated allogeneic myeloblasts remain in remission 79-132 weeks. Statistical analysis of the remission duration and survival of patients who received chemoimmunotherapy versus the control group shows highly significant differences.


Adjuvant immuno- and/or chemotherapy with neuraminidase-treated autogenous tumor vaccine and Bacillus Calmette-Guérin for head and neck cancers.


Active specific immunotherapy of human solid tumors. Active specific immunotherapy of human solid tumors by use of enzyme altered cells appears to be a feasible approach. Our initial results, we believe, warrant continued effort in this area. There seem to be no adverse clinical effects to such treatment. In vitro assay methods, to document enhanced immunity, must be included in any immunotherapy program. Equally importantly, such test methods should be expanded for the earliest detection of adverse effects, such as blocking during the course of immunotherapy. The role of immunotherapy must be that of adjuvant treatment, and its only applicability will be in that role.


Adjuvant immunotherapy in bronchogenic carcinoma. Ten patients with locally far advanced bronchogenic carcinoma were treated with autologous tumor vaccine after a radical surgical resection. Three of 10 patients treated with tumor vaccine are alive (median survival of 26 months) whereas all nine patients in the control group are dead (median survival of 6.5 months). Active immunotherapy adjunct to radical surgery appeared to improve cellular immunity of the treated patients in the postoperative period, and the migration inhibition test indicated sensitization of treated patients against their tumor.


Immunotherapy of human malignant melanoma with irradiated tumor cells, oral Bacillus Calmette-Guérin, and levamisole.


Immunotherapy of chronic myelocytic leukemia: effects of different vaccination schedules. In a clinical trial of immunotherapy in chronic myelocytic leukemia, 62 patients received repeated intradermal injections of BCG-cultured cell mixtures, while 16 were vaccinated with BCG alone. The lymphoblastoid cell lines used for vaccination were established from blood of patients with advanced myeloid leukemia and were reactive with "specific" primate antisera against myeloid leukemic cells. Both sensitization to target cell antigens and substantial general increases in delayed hypersensitivity responses were recorded among immunized patients. Major immunologic complications (hypersensitivity and "autoimmune" phenomena) were observed in 10 patients. These complications were attributable to the BCG content of vaccines, and their incidence correlated with intensity of immunologic stimulation. Data from cases in which intermittent busulfan therapy was used provided suggestive evidence that immunotherapy (either with BCG-cell mixtures or with BCG alone) prolonged unmaintained remissions in one-third of the patients. Among 48 "good-risk" patients, there was an inverse correlation between intensity of immunologic stimulation and survival. The survival of 18 patients who received the most intensive vaccination schedule was identical to that of controls. Survival of the other 30 patients was significantly better (p = 0.03), with an increase of 2 years in median survival. Survival of 30 poor-risk patients (24, most intensive vaccination schedule) was identical to that of controls. We conclude that immunologic stimulation may produce worthwhile prolongation of life in CML but that overly aggressive schedules of immunotherapy abrogate this effect. Our experience raises the question whether results in other clinical trials of immunotherapy may have been adversely affected by excessive frequency or dosage of immunologic stimulants.


Active immunization of children suffering from acute leukemia in remission with "living" mixed leukoblast vaccine and means of enhancement of antileukemic immunity.


Immunotherapy of osteosarcoma patients with virus-modified tumor cells. Twelve patients 11-20 years of age with recurrent osteosarcoma were immunized with either autologous or allogeneic tumor cells infected with influenza virus, strain B/Michigan or A/Port Chalmers. Six patients received only the vaccine, and the remaining six patients continued to receive methotrexate chemotherapy. The main objectives of this study were to determine if immunizations were toxic, if antibodies developed to the influenza virus antigen component of the vaccine, if this vaccine increased tumor-specific cellular and humoral immunity, and if the increase in immune response could be correlated with clinical course and prognosis. In all 12 cases, toxicity was negligible, and immunizations boosted antibody titers to both tumor cell and influenza virus antigens. However, in four of the six patients with advanced disease who received immunotherapy only, the vaccine did not stimulate mixed lymphocytes nor did it increase cell-mediated immunity. By contrast, five of six patients with minimal disease who continued methotrexate therapy developed cellular and humoral immunity in response to both allogeneic and autologous tumor cells. Although no clear-cut relationship between responses to the tumor cell vaccine and clinical course and prognosis could be demonstrated, three of the six patients with minimal disease have survived for 7-8 months after the first vaccination, without progression of disease. This study demonstrates that plasma membrane preparations derived from different lines of virus-infected osteosarcoma tumor cells will elicit an antibody response in patients with drug-resistant progressive osteogenic sarcoma.


Specific adoptive and passive immunotherapy be parabiosis for syngeneic mouse and rat tumors.


Comparison of allogeneic tumor vaccine with leukocyte transfer and transfer factor treatment of human cancer.


Adoptive transfer and specific active immunization of patients with malignant melanoma.


Immunotherapy of murine tumors with immune RNA.


Immunotherapy of cancer with immune RNA in animal models and cancer patients.


Discussion paper: tumor-specific transfer factor therapy in osteogenic sarcoma: a two-year study.


Preparation and therapeutic potential of rabbit antisera with "directed" specificities for mouse leukemias. Several immunization regimens for preparation of ALK-NABS were compared. One series of eight intravenous injections spaced over 5 weeks gave an ALK-NABS with potency and specificity that could be bettered only slightly by a second series of four injections spaced over 2 weeks, whereas a third series of injections was deleterious. Use of late immune antisplenocyte NABS for such immunizations produced ALK-NABS reagents with the highest in vitro specificity to leukemia cells relative to splenocytes after absorption, whereas early immune antisplenocyte NABS gave ALK-NABS with the highest antileukemia specificity relative to thymocytes. Therapy experiments with leukemias L1210 and BW-A showed increased survival times for isogeneic mice injected intraperitoneally with 10(3) (L1210 only), 10(4), and 10(5) (higher significance for L1210) cells, when ALK-NABS was given intraperitoneally in high dose on 4 or 5 successive days starting 1 day after inoculation of leukemia cells. In additional experiments with 10(5) cells given intraperitoneally, lower doses of ALK-NABS were progressively more effective with L1210 leukemia, producing some survivors without any apparent toxicity from the antiserum. In contrast, a similar experiment with leukemia BW-A was entirely negative. Addition of guinea pig serum to already excessive amounts of antiserum was not helpful.


Antibodies as carriers of radionuclides and cytotoxic drugs in the treatment and diagnosis of cancer.


Discussion paper: humoral immune responses to tumor-associated antigens.


Discussion paper: protective immunity in leukemic mice treated with specific "immunogenic" RNA. Mice were actively immunized against Friend leukemia virus tumorigenesis by vaccination with cell-free homogenates derived from infected splenocytes emulsified in Freund's adjuvant. Adoptive immunity was also achieved by transferring splenocytes from actively immunized donor animals intravenously into syngeneic recipient animals challenged with the virus. Furthermore, RNA-rich extracts derived from spleens of actively immunized donor animals were capable of transferring immunity to FLV leukemia when injected into recipient animals challenged with the virus. The "immune RNA," when incubated with normal splenocytes in vitro, followed by washing, resulted in a cell population that also induced adoptive immunity after transfer to normal animals challenged with virus either before, simultaneously with, or after injection of the treated splenocytes. RNase, but not DNase or other enzymes, inactivated the biologie activity of the protective RNA from immune donors. In addition, isogeneic mouse serum that contained neutralizing antibody to FLV also inhibited the protective effect of the specific RNA; sera from control mice immunized with unrelated antigens failed to neutralize the specific RNA. These results indicate that an RNA extract that contains a virus-associated or -induced antigen is formed in the spleens of actively immunized animals and possesses the ability to either directly induce protective immunity in recipient animals challenged with virus or, indirectly, to convert normal splenocytes in vitro to adoptively confer immunity to similar recipients. Further investigations concerning the mechanism by which such immunogenic RNA functions in vivo and in vitro, as well as the physicochemical nature of the RNA complex, especially that portion associated with the tumor virus-associated antigen, are needed.


Acute renal failure and gout as presenting features of acute lymphoblastic leukaemia. A leukaemic child is described who presented with renal failure and gout attributable to hyperuricaemia before the leukaemia could be diagnosed.


Progress in the treatment of adults with acute leukemia: review of regimens containing cytarabine studied by the Southwest Oncology Group.


The regulation of the jaw bite force in man.


Primary intimal sarcoma of pulmonary valve and trunk with osteogenic sarcomatous elements. Report of a case considered to be pulmonary embolus. A 49-year-old woman had a six-week history of increasing shortness of breath and fatigue. X-ray films and pulmonary scans showed multiple areas of emboli, especially in the right lung. Treatment with heparin was unsuccessful, and although a repeat scan showed only slight changes, the patient's condition deteriorated. Acute pulmonary edema and ventricular tachycardia preceded her death. Autopsy revealed a primary intimal sarcoma with osteogenic elements arising in the posterior leaflet of the pulmonary valve and obstructing the main pulmonary artery and its right branch.


Properties of Ca2+-, Mg2+-activated adenosine triphosphatase from rat incisor pulp.


Interrelationships between flow rate, amylase, calcium, sodium, potassium and inorganic phosphate in stimulated human parotid saliva.


Acute granulocytic leukemia: treatment of the disease.


Trace element content of surface and subsurface enamel relative to caries prevalence of the west coast of the United States of America.


Metabolism of carbohydrate in the major salivary glands of rats.


Ultrastructural study of human dental enamel using selected-area argon--ion-beam thinning.


The relationship between strontium in water supplies and human tooth enamel.


Lactate degradation by a strain of Neisseria isolated from human dental plaque.


Effect of fluoride on molecular size of proteoglycans in the rat incisor tooth.


Research in the toothpaste industry.

Research in the toothpaste industry.


A quantitative measure of mandibular joint dysfunction: phase plane modelling of jaw movement in man.


Small bowel perforation by a shield type intrauterine contraceptive device.


Dental caries prevalence in a heavy metal contaminated area of the West of England.


The work of women dentists.

The work of women dentists.


Root formation following traumatic loss of an immature incisor. A case report.


Hepatitis B and the dental surgeon.

Hepatitis B and the dental surgeon.


President's address at the opening of the forty-fourth session of the General Dental Council.


Treating Australia antigen positive patients. Practical experience.


Pitfalls in analysis of survival in clinical trials.


In vitro correlates of clinical response to methotrexate in actue leukaemia and Burkitt's lymphoma. The response of drug-resistant patients with acute leukaemia and Burkitt's lymphoma to treatment with a 24 h infusion of methotrexate (MTX) followed, in some cases,by cytosine arabinoside was correlated with in vitro measurements of total intracellular MTX, exchangeable intracellular MTX, and suppressibility of deoxyuridine (UdR) incorporation in isolated marrow blast cells at extracellular MTX concentrations of 10(-8)M, 10(-7)M, 10(-6)M and 10(-5)M. Total intracellular MTX levels and exchangeable intracellular MTX levels were not significantly different in responding or non-responding patients at any MTX concentration, but increased four-fold for every ten-fold concentration increment studied. Extracellular MTX levels in excess of 10(-7)M appeared necessary to allow accumulation of exchangeable intracellular MTX. UdR incorporation at 10(-6)M and 10(-5)M differed significantly between responding and non-responding patients, with responders having less than 20% of control values and non-responders having greater than 40% of control values. Further, increasing the extracellular MTX concentration from 10(-6)M to 10(-5)M produced no significant decrease in UdR incorporation in either group. The therapeutic implications of this apparent threshold are discussed.


Cell volume measurements in acute leukaemia: method and value for diagnosis and prognosis. Cell volume was measured using a Coulter counter in 42 cases of adult acute leukaemia, before any therapy. In every patient, the distribution was log-normal. A breakdown of the results with regard to the cell-type gives the following informations: The mean modal volume (M.M.V.) differs significantly from one type of leukaemia to another: the cell size in the myeloblastic type is larger than in the lymphoblastic, and smaller than in the monoblastic and myelomonocytic types. The dispersion of cell volumes, for a single patient, is low in acute lymphoblastic leukaemia, wider in myeloblastic cases and is even larger in myelo-monocytic patients. In 9 of the 10 acute myelo-monocytic leukaemias studied, the existence of two populations was shown by a double peak. Once relapse occurs, the cell volumes seem greater than during the first phase of the disease, at least in acute lymphoblastic leukaemia. No correlation has been found between the mean modal volumes and the labeling index, after incorporation of 3H-TdR.


Specific xenogenous antiserum to cells of chronic myeloid leukemia (CML) in blastic crisis. The antiserum was obtained from horses immunized with cells from patients with blastic crisis of CML and completely absorbed with normal white blood cells (WBC). The absorbed antiserum remained cytotoxic to blast cells from nearly half of the patients in blastic crisis and did not react with WBC from patients with Acute Myeloid Leukemia (AML), Acute Lymphoid Leukemia (ALL), Chronic Lymphoid Leukemia (CLL) and Chronic Myeloid Leukemia (CML) in its chronic phase as well as with cells of human normal bone marrow or fetal liver.


A simplified in vitro classification for prognosis in adult acute leukemia: the application of in vitro results in remission-predictive models. Previous classification in vitro of adult acute leukemia incorporating morphology has been complex and difficult to understand. We have devised a simplified classification based solely on leuekemic proliferation in vitro. Seventy-six patients with adult acute leukemia previously untreated were included in this study and received identical chemotherapy. Three groups were recognized. The complete remission rate was 76% in the 21 patients with no leukemic growth in vitro (Group 1), 75% in 36 patients with leukemic cell growth but aggregates of 20 cells or less (Group 2), and only 21% in the 15 patients with aggregates of greater than 20 (Group 3). There was a highly significant difference in complete remission rates between Group 3 and the other two groups (p less than 0.001). Linear logistic regression analysis demonstrated the independence of the growth in vitro from other prognostic variables. A predictive model utilizing the in vitro result more accurately predicted for remission, both retrospectively and prospectively, than a model constructed with presently known prognostic parameters. The cause of death in failures suggested that this system detects resistance to the chemotherapy.


Chemo-immunotherapy versus chemotherapy in acute myeloid leukemia. Preliminary results. Since November 1974, 44 patients with acute myeloid leukemia, in first remission were randomized between chemotherapy alone and chemotherapy plus BCG. There were 8 relapses and 7 deaths with chemotherapy, 7 relapses and 3 deaths with chemotherapy plus BCG. The survival of both groups is not, at the time, significantly different.


The National Health Planning and Resources Act of 1974 (Public law 93-641).


Transducer characteristics for ultrasonic stereoholography.


Primary malignant tumours of bone.

Primary malignant tumours of bone.


Diseases of the alimentary system. Anorexia and loss of weight.


Erythroleukemia-like syndrome due to busulfan toxicity in polycythemia vera. Over a 19-year period, a patient with polycythemia vera who had undergone a splenectomy received six courses of busulfan for recurrent thrombocytosis. The total dose of busulfan given for the sixth course was greater than that used for the previous ones. Severe pancytopenia followed, which persisted for 4 months. During this period there was marked erythroid hyperplasia in the bone marrow with striking dyserythropoiesis; PAS-positive red cell precursors, as well as moderate numbers of circulating normoblasts and evidence of chronic and acute hemolysis, were present. All of these findings reverted to normal without therapy, and the polycythemic state eventually recurred. These events are interpreted as an unusual marrow reaction following busulfan overdosage rather than a transient erythroleukemia.


A case of chronic granulocytic leukemia in a dog. A case of chronic granulocytic leukemia was diagnosed in a ten year old miniature poodle and was observed for four and one half years. Methods of diagnosis and characteristic features are described. A persistent granulocytosis with a preponderance of mature forms and the absence of a detectable underlying pyogenic process were key diagnostic features which enabled distinction of this neoplastic process from acute granylocytic leukemia and a leukemoid reaction. Other features included dysplastic granulocytes in various developmental stages, marginal anemia and hyperplastic bone marrow (myeloid elements). No blast crisis occurred. This dog was euthanatized in August 1975.


Telangiectatic osteogenic sarcoma.

Telangiectatic osteogenic sarcoma. Of approximately 1,999 cases of osteogenic sarcomas at the Mayo Clinic, 25 were diagnosed as telangiectatic osteogenic sarcomas. Of the 25 patients involved, 16 were males and 9 were females, and their ages ranged from 6 to 49 years. Six patients had had pathologic fracture. The lesions were typically located centrally and usually in the distal femur or proximal humerus and roentgenographically were large and purely lytic with destruction of cortex. Grossly, the lesions were cystic and contained clotted blood. Histologically, cystic spaces that contained blood were lined with anaplastic spindle cells and benign giant cells; sometimes, there were so few malignant cells that diagnosis was difficult. Usually, fine, lacelike osteoid was present. Of the 25 patients, 23 have died of metastatic disease, and another has developed pulmonary metastasis 11 months after amputation. Only one patient has survived for more than five years; however, he has developed pneumothorax. Data from this series suggest that the outlook in telangiectatic osteogenic sarcoma is more bleak than in conventional osteosarcoma.


Occurrence of acute leukemia in females in a genetically isolated population. Acute lymphoblastic leukemia was found in six young females in a genetically isolated Syrian Jewish Community in Brooklyn, N.Y. over a 15-year period. This represents a frequency 30 times greater than the expected rate. In this community the frequency of first cousin marriages is estimated to be seven percent. Three cases were related on their maternal side, the parents of a fourth case were themselves related as were both sets of grandparents of a fifth case. In two families a history of infertility was present. On average, fathers of the cases were 5.5 years older at birth of the cases than a matched sample of community controls and 7.2 years older than a matched sample of non-community controls. The high frequency of consanguinity and the older age of the fathers may increase risk to acute leukemia for young girls in this community.


Simultaneous occurrence of non-Hodgkin's lymphoma and acute myelomonocytic leukemia. The simultaneous occurrence of nodular poorly differentiated lymphocytic lymphoma (NLPD) and acute myelomonocytic leukemia (AMML) was confirmed by the histologic examination of lymph node section, peripheral blood, and bone marrow. This association in the absence of previous chemotherapy or radiotherapy has not been previously documented. There have been six previous case reports of patients with non-Hodgkin's lymphocytic lymphoma who, during treatment with alkylating agents or radiotherapy, developed acute myeloid leukemia (AML). These methods of therapy may have had a leukemogenic role in such patients. The possible relationship between these two diseases is discussed.


Accumulation of giant heterogeneous RNA molecules in acute myeloid leukemia blast cells. Time course and "chase" experiments showed that, after incubation of acute myeloid leukemia blast cells with a labeled RNA precursor, a large proportion of radioactivity remained associated with RNA molecules larger than 45 S even after several hr. Double-labeling experiments with [5-3H]uridine and [methyl-14C]methionine indicated that unmethylated giant heterogeneous RNA larger than 45 S is processed much more slowly than the 45 S ribosomal precursor, so that relatively large amounts of fairly stable RNA of the former class accumulate in the cell. The measurement of labeled giant heterogeneous RNA molecules bound to polyuridylate-fiberglass filters showed that molecules carrying polyadenylate segments seemingly turn over faster than those lacking polyadenylate.